Chemical carcinogenesis via benzo[alpha]pyrene is the archetypal model for the carcinogen induction of tumors. BP is metabolized to diol epoxides (BPDE) that covalently bind to conformation with the failure of normal DNA processing. Ample studies of these stereochemically homogeneous deoxynucleosides-BPDE derivatives are essential for continuing BPDE carcinogenesis studies, however present methods are unable to deliver sufficient quantities. The objective of these proposed studies is the development of new methods for the preparation of diastereomerically pure, BPDE-deoxynucleoside adducts for these studies. We propose to improve to improve both the preparation of nonracemic BPDE as well as introduce a novel, general method for its coupling into both cis and trans BPDE- deoxynucleoside adducts. Two independent strategies are proposed for improving BPDE synthesis: (i) a novel, pi-stacking strategy for the diastereoselective synthesis of non-carcinogenic intermediates and (ii) the asymmetric epoxidation of 9,10-dihydro BP, which will be efficiently converted to BPDE by known synthetic steps. As a second thrust of this research program, we will investigate the amination of 7,8-epoxy-7,8,9,10- tetrahydro BP with deoxynucleoside exocyclic amino functions. These efforts are a model for the later synthesis of BPDE-modified deoxynucleosides and modified-oligodeoxynucleotides. We will broaden the scope of the findings in these studies to the preparation of related polycyclic aromatic hydrocarbon diol epoxides (e.g. naphthalene, phenanthrene, etc.) and their covalent addition products with DNA. As an important byproduct of this program, we will establish a firm foundation for the design and implementation of stereoselective methods that incorporate pi-pi interactions.